Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia

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This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.

Condition or disease

Intervention/treatment

Phase

SchizophreniaPsychotic Disorders

Drug: PimozideDrug: Placebo

Phase 4

Detailed Description:

A significant number of schizophrenics exhibit partial or no response to typical antipsychotic medications. Clozapine has been shown to be more effective in treating schizophrenia than typical antipsychotic drugs. However, only an estimated 30% to 60% of people who are unresponsive to treatment with typical antipsychotics will respond to treatment with clozapine. Taking clozapine with pimozide, an antipsychotic drug, can increase clozapine's effects. However, sufficient research on this approach has not yet been performed. This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.

Participants in this double-blind study will receive a stable dose of clozapine for eight weeks prior to enrollment. For the first 4 weeks following enrollment, baseline measurements will be taken. Once a week, participants will report to the study site, where symptom severity, cognitive ability, and functional status, including reading level, will be assessed. In addition, participants will receive a standard medical examination, which will include blood tests and an EKG. Upon completion of this initial phase, participants will be randomly assigned to one of two treatment groups: clozapine combined with pimozide; or clozapine combined with placebo. This phase will last for 12 weeks. Study visits will continue to occur weekly, and will be used to re-assess the measurements obtained during baseline. In addition, participants will have an EKG at each study visit for the first 4 weeks of treatment. All baseline measurements will be repeated in Week 12.

Participants will receive encapsulated placebo made to match active drug

Drug: Placebo

Active drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment.

Other Name: Sugar Pill

Experimental: pimozide

Participants will receive pimozide flexible dosing

Drug: Pimozide

Each capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects.

The Clinical Global Impression-improvement (CGI-improvement) scale is a research rating tool, developed for use in NIMH-sponsored clinical trials provides a brief assessment of the clinician's view of the patient's overall clinical improvement prior to and after initiating a study medication. The CGI-change is rated on a seven point scale ranging from 1= very much improved since the initiation of treatment to 7=very much worse since the initiation of treatment. Therefore, a lower score indicates more improvement in symptoms over time.

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Ages Eligible for Study:

18 Years to 65 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of schizophrenia according to DSM-IV criteria

Any schizoaffective disorder or subtype

Score greater than 60 on the Positive and Negative Syndrome Scale (PANSS)

Currently taking clozapine

Score of four or higher on two or more items from the positive symptom subscale of the PANSS

Score of 4 or greater on the Clinical Global Impression (CGI) scale

Clozapine plasma level greater than 378 µg/ml

Stable dose of clozapine demonstrated to have been associated with a clozapine plasma level greater than 378 µg/ml for at least eight weeks

Able to read at an 8th grade level or above

Exclusion Criteria:

History of unstable coronary artery disease

Congestive heart failure

History of long Q-T syndrome

History of cardiac arrhythmia

History of cardiac conduction delay

Baseline QT correction score greater than 0.425 seconds

Liver disease

History of stroke

History of Neuroleptic Malignant Syndrome

Hypokalemia

Hypocalcemia

Current blindness, deafness, language difficulties, or any other disability which may prevent participation or cooperation in the study

Current suicidal or homicidal thoughts

Currently abusing psychoactive substances

Currently receiving antidepressants, thymoleptics, L-DOPA, buspirone, or antipsychotics other than clozapine (Valproic acid and Divalproex sodium are not criteria for exclusion)